Patient-derived organoids from endometrial disease capture clinical heterogeneity and are amenable to drug screening.

Autor: Boretto M; Laboratory of Tissue Plasticity in Health and Disease, Stem Cell and Developmental Biology Cluster, Department of Development and Regeneration, KU Leuven, Leuven, Belgium. matteo.boretto@kuleuven.be., Maenhoudt N; Laboratory of Tissue Plasticity in Health and Disease, Stem Cell and Developmental Biology Cluster, Department of Development and Regeneration, KU Leuven, Leuven, Belgium., Luo X; Stem Cell Institute Leuven, Department of Development and Regeneration, KU Leuven, Leuven, Belgium., Hennes A; Laboratory of Endometrium, Endometriosis and Reproductive Medicine, Department of Development and Regeneration, KU Leuven, Leuven, Belgium., Boeckx B; Center for Cancer Biology, VIB, Leuven, Belgium.; Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium., Bui B; Laboratory of Tissue Plasticity in Health and Disease, Stem Cell and Developmental Biology Cluster, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.; Woman and Baby Division, Reproductive Medicine, University Medical Centre Utrecht (UMCU), Utrecht, The Netherlands., Heremans R; Laboratory of Tissue Plasticity in Health and Disease, Stem Cell and Developmental Biology Cluster, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.; Woman and Child Cluster, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.; Gynecology and Obstetrics, University Hospitals Leuven (UZ Leuven), Leuven, Belgium., Perneel L; Laboratory of Tissue Plasticity in Health and Disease, Stem Cell and Developmental Biology Cluster, Department of Development and Regeneration, KU Leuven, Leuven, Belgium., Kobayashi H; Laboratory of Tissue Plasticity in Health and Disease, Stem Cell and Developmental Biology Cluster, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.; Department of Anatomy and Structural Science, Faculty of Medicine, Yamagata University, Yamagata, Japan., Van Zundert I; Laboratory of Molecular Imaging and Photonics, Department of Chemistry, KU Leuven, Leuven, Belgium., Brems H; Laboratory for Neurofibromatosis Research, Department of Human Genetics, KU Leuven, Leuven, Belgium., Cox B; Laboratory of Tissue Plasticity in Health and Disease, Stem Cell and Developmental Biology Cluster, Department of Development and Regeneration, KU Leuven, Leuven, Belgium., Ferrante M; Unit of Translational Research in Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium., Uji-I H; Laboratory of Molecular Imaging and Photonics, Department of Chemistry, KU Leuven, Leuven, Belgium., Koh KP; Stem Cell Institute Leuven, Department of Development and Regeneration, KU Leuven, Leuven, Belgium., D'Hooghe T; Woman and Child Cluster, Department of Development and Regeneration, KU Leuven, Leuven, Belgium., Vanhie A; Laboratory of Endometrium, Endometriosis and Reproductive Medicine, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.; Leuven University Fertility Center (LUFC), UZ Leuven, Leuven, Belgium., Vergote I; Woman and Child Cluster, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.; Gynecology and Obstetrics, University Hospitals Leuven (UZ Leuven), Leuven, Belgium., Meuleman C; Laboratory of Endometrium, Endometriosis and Reproductive Medicine, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.; Leuven University Fertility Center (LUFC), UZ Leuven, Leuven, Belgium., Tomassetti C; Laboratory of Endometrium, Endometriosis and Reproductive Medicine, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.; Leuven University Fertility Center (LUFC), UZ Leuven, Leuven, Belgium., Lambrechts D; Center for Cancer Biology, VIB, Leuven, Belgium.; Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium., Vriens J; Laboratory of Endometrium, Endometriosis and Reproductive Medicine, Department of Development and Regeneration, KU Leuven, Leuven, Belgium., Timmerman D; Woman and Child Cluster, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.; Gynecology and Obstetrics, University Hospitals Leuven (UZ Leuven), Leuven, Belgium., Vankelecom H; Laboratory of Tissue Plasticity in Health and Disease, Stem Cell and Developmental Biology Cluster, Department of Development and Regeneration, KU Leuven, Leuven, Belgium. hugo.vankelecom@kuleuven.be.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2019 Aug; Vol. 21 (8), pp. 1041-1051. Date of Electronic Publication: 2019 Aug 01.
DOI: 10.1038/s41556-019-0360-z
Abstrakt: Endometrial disorders represent a major gynaecological burden. Current research models fail to recapitulate the nature and heterogeneity of these diseases, thereby hampering scientific and clinical progress. Here we developed long-term expandable organoids from a broad spectrum of endometrial pathologies. Organoids from endometriosis show disease-associated traits and cancer-linked mutations. Endometrial cancer-derived organoids accurately capture cancer subtypes, replicate the mutational landscape of the tumours and display patient-specific drug responses. Organoids were also established from precancerous pathologies encompassing endometrial hyperplasia and Lynch syndrome, and inherited gene mutations were maintained. Endometrial disease organoids reproduced the original lesion when transplanted in vivo. In summary, we developed multiple organoid models that capture endometrial disease diversity and will provide powerful research models and drug screening and discovery tools.
Databáze: MEDLINE
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